HIF mediates changes in gene expression in response to changes in cellular oxygen concentration. HIF is a heterodimer having an oxygen-regulated subunit (HIF-α) and a constitutively expressed subunit (HIF-β). In cells with adequate oxygen, HIF-α is hydroxylated at conserved proline residues by prolyl-hydroxylase (PHD) resulting in its rapid degradation. In cells with inadequate oxygen (hypoxia), there is a rapid accumulation of HIF-α which triggers an increase in glycolysis to compensate for energy loss due to reduced oxidative phosphorylation and upregulation of erythropoiesis and angiogenesis to achieve more efficient oxygen utilization. Other HIF-independent signalling pathways also respond to hypoxia and contribute to oxygen availability increase. PHD exists in three isoforms referred to as PHD1, PHD2 and PHD3 which function as oxygen sensors and in the regulation of cell metabolism in response to oxygen content in cells. Due to the central role of PHD in oxygen sensing, PHD inhibitors would be expected to be useful in treating cardiovascular disorders such as ischemic events, hematological disorders such as anemia, pulmonary disorders, brain disorders, and kidney disorders.
Studies using genetically engineered knockout mice or siRNA have identified that the three PHD isoforms differ in the way that they regulate HIF. It would appear that PHD inhibitors with an activity profile showing selectivity towards PHD1 may be most advantageous as unwanted side effects can arise from significant inhibition of PHD2.    Patent Document 1 describes certain triazolopyrimidine derivative compounds that are said to be useful as pest control agents.    Patent Document 2 describes certain pyridyl triazolopyrimidine derivative compounds that are said to be useful as harmful organism control agents.    Patent Document 3 describes triazolopyrimidine compounds that are said to be useful for treating of inhibiting the growth of cancerous tumour cells and associated diseases.    Patent Document 4 describes certain triazolopyrimidine compounds that are said to be useful as anxiolytic agents.    Non-Patent Documents 1 and 2 describe triazolopyrimidine compounds.